diff --git a/doc/source/whatsnew/v0.25.0.rst b/doc/source/whatsnew/v0.25.0.rst
index 8e72ce83ac028..cae73386bc1e1 100644
--- a/doc/source/whatsnew/v0.25.0.rst
+++ b/doc/source/whatsnew/v0.25.0.rst
@@ -205,7 +205,7 @@ Interval
 Indexing
 ^^^^^^^^
 
--
+- Improved exception message when calling :meth:`DataFrame.iloc` with a list of non-numeric objects (:issue:`25753`).
 -
 -
 
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 623a48acdd48b..46904e32f88a6 100755
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -13,7 +13,7 @@
 
 from pandas.core.dtypes.common import (
     ensure_platform_int, is_float, is_integer, is_integer_dtype, is_iterator,
-    is_list_like, is_scalar, is_sequence, is_sparse)
+    is_list_like, is_numeric_dtype, is_scalar, is_sequence, is_sparse)
 from pandas.core.dtypes.generic import ABCDataFrame, ABCPanel, ABCSeries
 from pandas.core.dtypes.missing import _infer_fill_value, isna
 
@@ -2075,10 +2075,15 @@ def _validate_key(self, key, axis):
             # so don't treat a tuple as a valid indexer
             raise IndexingError('Too many indexers')
         elif is_list_like_indexer(key):
-            # check that the key does not exceed the maximum size of the index
             arr = np.array(key)
             len_axis = len(self.obj._get_axis(axis))
 
+            # check that the key has a numeric dtype
+            if not is_numeric_dtype(arr.dtype):
+                raise IndexError(".iloc requires numeric indexers, got "
+                                 "{arr}".format(arr=arr))
+
+            # check that the key does not exceed the maximum size of the index
             if len(arr) and (arr.max() >= len_axis or arr.min() < -len_axis):
                 raise IndexError("positional indexers are out-of-bounds")
         else:
diff --git a/pandas/tests/indexing/test_iloc.py b/pandas/tests/indexing/test_iloc.py
index 7147757953b01..27f62af8394ef 100644
--- a/pandas/tests/indexing/test_iloc.py
+++ b/pandas/tests/indexing/test_iloc.py
@@ -118,6 +118,21 @@ def check(result, expected):
         with pytest.raises(IndexError, match=msg):
             dfl.iloc[:, 4]
 
+    @pytest.mark.parametrize("index,columns", [(np.arange(20), list('ABCDE'))])
+    @pytest.mark.parametrize("index_vals,column_vals", [
+        ([slice(None), ['A', 'D']]),
+        (['1', '2'], slice(None)),
+        ([pd.datetime(2019, 1, 1)], slice(None))])
+    def test_iloc_non_integer_raises(self, index, columns,
+                                     index_vals, column_vals):
+        # GH 25753
+        df = DataFrame(np.random.randn(len(index), len(columns)),
+                       index=index,
+                       columns=columns)
+        msg = '.iloc requires numeric indexers, got'
+        with pytest.raises(IndexError, match=msg):
+            df.iloc[index_vals, column_vals]
+
     def test_iloc_getitem_int(self):
 
         # integer